This document provides an overview of integrated approaches to health from the scientific community in the Occitanie region of France. It discusses how integrated health looks at human health as interconnected with animal and environmental health. It describes the factors involved in disease emergence and transmission, including pathogens, reservoirs, vectors, interfaces, and mechanisms of change over time. The scientific community in Occitanie studies these factors across human, animal, plant and environmental health through various research laboratories. The document also discusses how integrated approaches consider food systems and global health.
VIP Call Girls Service Miyapur Hyderabad Call +91-8250192130
Global health approaches in Occitanie
1. AGROPOLIS
INTERNATIONAL
les dossiers
Expertise of the scientific community
in the Occitanie area (France)
d
Number 25
December 2019
Global health
People, animals, plants, the environment:
towards an integrated approach to health
‘
3. Over the last 40 years, the recurrence of epidemics
resulting from known or new infectious
agents (AIDS, avian influenza, SARS, Ebola,
etc.) has sharply raised awareness about the
interconnections between human health and the
health of animals and the environment, as well as
the effects of global changes on these interactions.
In line with the emerging trends in other scientific
fields, systemic thinking, strategies and practices
have gained ground in the area of health. In this
25th
dossier d’Agropolis, we offer an overview
of the expertise of the scientific community in
the French region of Occitanie in the manifold
areas of health and of the systemic approaches
being developed. Bringing together a critical mass
of research in medicine, agronomy, veterinary
science and ecological, environmental and social
science, this diverse community is fertile terrain
for adopting an integrated approach to health and
developing innovative concepts and methods.
While far from exhaustive, this report provides
illustrative examples of research undertaken by
scientific teams in the region alongside partners
in France, its overseas territories, and around the
world. All aspects affecting health are considered:
not only human and animal health, but plant
health, the environment, and issues linked to diet
and food production. No less than 66 research
units are cited in this report, illustrating the
diversity and complementarity of the scientific
work being carried out from this hub of integrated
health research.
Patrick Caron,
Chair of Agropolis International
Global health
People, animals, plants, the environment:
towards an integrated approach to health
2Introduction
22
32
42
48
Analysing, preventing and controlling epidemics:
integrated health approaches in action
Food, planet, health: the global health concept
applied to food systems
Research, education and training in integrated
health in Occitanie
References
4
Factors in the emergence and transmission of infectious
diseases: the elements for an integrated approach
to health
6
8
10
12
17
22
25
28
1. Understanding and characterising pathogens
2. Understanding and characterising pathogen reservoirs
3. Understanding and characterising disease vectors
4. Understanding and characterising interfaces
5. Understanding and characterising emergence mechanisms
1. Creating a favourable collaborative environment
2. Bringing together different disciplines and stakeholders
in the analysis and management of health risks
3. Combatting antimicrobial resistance requires integrated
approaches
34
36
38
42
46
1. Food and nutrition security and health
2. Food safety and health
3. Integrated health applied to food systems
1. The organisations involved in integrated health research
2. Education and training in integrated health approaches
1
4. A
t the turn of the 21st century, a trend for
considering health in a more integrated way
emerged.Taking a more holistic perspective,
these integrated approaches identify human health as
interconnected with the health of animals and of the
environment.This relatively recent upsurge of interest
does not mean these human–animal–environment links
are new: hunter-gatherers could contract diseases from
hunted animals, though it was the domestication of wild
species that created the first major epidemiological
bridge between animal and human populations with
an impact on health1
.The unceasing expansion and
progression of animal production systems since then
has continued to create contexts that favour the
emergence and transmission of pathogens between
animals and humans. But at the end of the 20th century,
the emergence of known or unknown infectious agents –
AIDS, avian influenza, severe acute respiratory syndrome
(SARS) and, more recently, Ebola in Africa – accelerated2
.
The factors involved in this phenomenon reflect global
changes driven by human activities around the planet:
habitat destruction, degradation of natural ecosystems,
biodiversity loss, intensification of livestock and crop
farming, urbanisation, increased and unprecedented
contact between people and wild and domesticated
species, climate change that is disrupting certain
ecological processes, air and sea transport connecting
previously independent ecosystems, etc.
This complexity and the new epidemiological dynamics
where humans–livestock–wildlife–the environment
intersect are at the centre of the integrated approaches
that have sprouted during recent health crises. In its
narrowest definition, the ‘One Health’ concept promotes
an integrated approach for studying zoonotic diseases
(diseases and infections caused by agents that spread
naturally between vertebrate animals and people and vice
versa) in order to improve public health.The ‘EcoHealth’
concept considers the health of people, animals and the
state of ecosystems, with more of a focus on the links
between biodiversity and health. Lastly, the ‘Planetary
Health’ concept takes into account the physical and
biological limitations of the Earth in defining the niche in
which health, well-being and human equality can develop,
taking into account political, economic and social aspects
(see box opposite)3
.This notion of ‘Planetary Health’ –
or ‘Global Health’ – offers an analytical framework for
exploring the interrelationships between human activities
and well-being in a context of long-term sustainability: a
framework that the scientific community studying food
systems is starting to adopt. In line with this paradigm
shift, an article published by the EAT-Lancet Commission
at the beginning of 2019 argued for ‘a healthy diet derived
from sustainable production methods’, marking the first
attempt at a definition of a set of universal goals to
develop a food system that supports human health and
environmental sustainability4
.
While these systemic approaches differ in scope, they
share a strategy of building bridges between different
disciplines, of investigating different spatial and temporal
scales, of enlarging the pool of shared knowledge,
of implementing cross-sectoral solutions, and of co-
constructing management methods that involve all
stakeholders (e.g. through action research), taking into
account issues such as gender equality and social justice.
These principles are not specific to the field of health;
they can be applied to any complex system that includes
human populations. One example is natural resource
management, a field that was an early adopter of this
approach5
. Educational programmes for future experts
in all fields concerned should be designed to take these
principles into account.
The scientific community in the French region of
Occitanie brings together a critical mass of research in
medicine, agronomy, veterinary science, and ecological,
environmental and social sciences, making it a fertile
terrain for adopting such approaches and developing
innovative concepts and methods.This dossier aims to
illustrate some of the work carried out, from the study
of the mechanisms behind the emergence of epidemics,
through the implementation of integrated health
approaches to prevent and control these outbreaks, to
the analysis of the links between human health and diet
in all its aspects: nutrition, food security, food safety (both
quality and toxicology), and the environmental impact of
food production.The final section presents the region’s
scientific environment, including its multiple institutes and
research units (referred to by their ACRONYMS in the
text, see pages 44-45 for information on the research
units) and the educational and training programmes
offered on integrated health approaches.
Introduction
22
One
Health
Preventive
veterinary
medicine
Environment
Pe
ople
Anim
als
One
medicine
Environmental
health
5. Definitions of health
According to the World Health Organisation, human health is not only
a question of the absence of disease or disability, but is a state of physical,
mental and social well-being and a fundamental human right.
Public health concerns the collective management of the health of a
population in its community, whether this involves treatment, prevention,
education or social hygiene.
International health is the branch of public health focused on the
specific issues of developing countries and the aid efforts of industrialised
countries.
Global health is a field of study, research and practice that prioritises
improving health and achieving health equity for everyone in the world.
Environmental health covers aspects of human health, including
quality of life, that are determined by physical, chemical, biological, social,
psychosocial and aesthetic factors of the environment.
Animal health concerns both domesticated animals (pets and livestock)
and wild animals.It is at once an ethical,economic and health issue as many
diseases are zoonotic (i.e. can be transmitted to humans).
The area of veterinary public health covers all activities directly or
indirectly related to animals (or animal products or by-products) that
contribute to the protection, preservation and improvement of human
health.
Plant health is a field that focuses on crop pests and diseases (pathogens,
insect pests, etc.) that compromise harvests in terms of quantity or quality,
as well as methods of crop protection.
Ecosystem healthcan be defined as a social cross-disciplinary construction
which characterises the state of a socio-ecosystem in relation to the array
of services that are expected from it.
Integrated health approaches3
The One Health concept puts the emphasis
on the relationships between human health,
animal health and ecosystems,bridging ecology
and human and veterinary medicine.The One
Health approach focuses mainly on infectious
diseases, whether these are transmitted
from animals to humans or vice versa, on the
emergence of these diseases in relation to
global changes,on antimicrobial resistance,and
on food safety.
The EcoHealth concept promotes an
ecosystem approach to health, focusing
primarily on environmental and socio-
economic issues.It was originally formulated by
ecologists specialising in diseases and working
in the field of biodiversity conservation.
The Planetary Health concept takes into
account the planet’s environmental limits –
physical and biological – within which human
health, well-being and equality can flourish by
examining issues from a political,economic and
social point of view. In sum, planetary health
– or global health – considers the health of
human civilisation and the state of the natural
systems on which it depends.
3
Integrated approaches to health
Ecosystem
Planet
Environment
Anim
al
s
People
Plants
7. 5
While this section focuses on zoonotic diseases, it
equally pertains to the emergence and transmission of
infectious diseases whether they affect people, animals
or plants, as the mechanisms involved are the same, no
matter the host.The scientific community in Occitanie
is investigating the multiple facets of the pathogen–host
relationship for a spectrum of hosts (humans, livestock,
pets, wild animals, cultivated and wild plants) and a
wide range of pathogenic agents (viruses, bacteria,
protozoan and metazoan parasites, prions) responsible
for a multitude of diseases (see the table below for
examples of some of those affecting humans).The
region’s laboratories, many of which are nationally or
internationally recognised, are conducting research at
different spatial and temporal scales to gain knowledge
on these multifaceted levels in order to meet the
scientific and social challenges around infectious
diseases.
Aside from infectious diseases, viruses, bacteria and
parasites are also responsible for around one out of six
cancers in humans worldwide. For example, one out of
two cases of cervical cancer is attributable to the human
papillomavirus, and 80% of cases of liver and stomach
cancer are caused by infections (particularly the hepatitis
B and C viruses). Some of these oncogenic viruses are
studied in Occitanie laboratories: IRIM specialises in
retroviruses, such as the human T-lymphotropic virus,
which causes a form of leukaemia, and the murine
leukaemia virus, which affects rodents and is used as a
study model, and MIVEGEC and PHARMA-DEV are
studying the ecology and evolution of papillomaviruses.
Some pathogenic agents affecting humans
studied by the scientific community in Occitanie
Pathogen and mode of transmission Disease Laboratory accreditation
Viruses: infectious agents that require a host, often a cell, whose metabolism and constituents they use to multiply. In their extracellular form, viruses consist of a core of nucleic acid (DNA or RNA) generally
surrounded by a protein coat (a capsid).
Virus transmitted directly (e.g. hepatitis A, C, E, HIV, influenza, Ebola, etc.) Hepatitis, AIDS, flu, Ebola haemorrhagic fever
CPTP is a national reference centre for the hepatitis A and E virus
TRANSVIHMI is a reference laboratory for the World Health
Organisation for HIV
ASTRE is a national reference centre for the Rift Valley fever
Virus transmitted to mammals by mosquitoes (e.g. dengue, Zika,West Nile virus,
Usutu, Chikungunya, etc.)
Fevers, haemorrhagic fevers, arthropathy, encephalitis, microcephaly
Virus transmitted by a vector or directly (e.g. Bunyaviridae) Rift Valley fever, Crimean-Congo haemorrhagic fever
Viruses whose transmission mechanisms are still not well known (e.g. Coronavirus) Middle East respiratory syndrome
Bacteria: living microscopic organisms, most often unicellular (sometimes multicellular in the case of filamentous bacteria), whose cells have no nucleus (i.e. prokaryotic organisms). Most species of bacteria do not live
individually in suspension, but in complex communities embedded in a mucosal gel (or biofilm) that adheres to a surface.
Escherichia coli Enteropathy
IRSD participates in expert committees for the French National
Agency for Public Health and the National Health & Safety Agency
for Food, the Environment and Work (Anses)
VBMI is a national reference centre for Brucella
Vibrio Cholera, enteropathy
Staphylococcus Food poisoning, local infections
Mycobacterium Tuberculosis
Mycoplasma Pneumonia
Brucella Brucellosis
Leptospira Leptospirosis
Borrelia (transmission by vector: ticks) Borreliosis, Lyme disease
Protozoans: unicellular organisms whose cells have a nucleus and which live exclusively in water, moist soil or inside another organism.
Plasmodium (transmission by vector: mosquitoes) Malaria
MIVEGEC is a national reference centre for Toxoplasma and
Leishmania
INTERTRYP is a reference laboratory for the World Organisation
for Animal Health and a collaborating centre for the World Health
Organisation for trypanosomiasis
Toxoplasma (transmitted directly) Toxoplasmosis
Trypanosoma (transmission by vector: flies, bedbugs, leeches)
Sleeping sickness, nagana (African animal trypanosomiasis), Chagas
disease
Leishmania (transmission by vector: phlebotomine sand flies) Leishmaniasis
Babesia (transmission by vector: ticks) Babesiosis
Parasitic worms: multicellular eukaryotic organisms belonging to diverse groups such as the helminths (flatworms), trematodes (blood flukes) and nematodes (roundworms).
Schistosomes Schistosomiasis (bilharzia)
IHPE has the world’s largest collection of living strains of
schistosomes
Nematodes (transmitted directly and by vector: black flies, deer flies, mosquitoes) Gastrointestinal parasites, filariasis
Taenia tapeworms (transmitted directly) Cysticercosis
Prions: pathogenic agents consisting of a misfolded protein that, in contrast to infectious agents such as viruses, bacteria or parasites, do not contain nucleic acid (DNA or RNA) that carries the infectious information.
Prions (transmitted directly) Transmissible spongiform encephalopathies
12. 10
Some pathogenic agents are transmitted from one
vertebrate (human or animal) to another by the
intermediary of a vector, generally a blood-sucking
arthropod (e.g. mosquito, tick, sand fly, tsetse fly, etc.).
Understanding the biology and ecology of these vectors
is a third keystone in integrated approaches to health.
A vector is infected when it bites a host carrying the
pathogen; it then transmits the infectious agent to a new
host at its next feeding. Some Flaviviruses borne by Aedes
mosquitoes (e.g. dengue, Chikungunya, Zika) are also
transmitted by female mosquitoes to their descendants,
due to the ability of these viruses to persist for several
months in mosquito eggs.Vectors are also hosts and
reservoirs of pathogens. For example, parasites of the
Plasmodium genus, the causative organism of malaria,
carry out their sexual reproduction cycle in the intestine
of the mosquito, making the latter, from a biological
point of view, the definitive host. For certain arboviruses
(arthropod-borne viruses), mammals are an intermediate
host – sometimes accidental, sometimes as an amplifier,
or sometimes as an epidemiological dead end, when
vector transmission between mammals is impossible: this
is the case, for example, with the West Nile fever virus,
whose main hosts are birds (see diagram above).
Insects and mites that are disease vectors generally have
elevated evolutionary potential due both to a short
generation time and a mode of sexual reproduction that
maintains high genetic diversity in natural populations.
They adapt rapidly to changes in the environment,
demonstrating a certain plasticity and allowing them to
colonise new ecological niches or to become resistant
to treatments (insecticides or acaricides).This capacity
to evolve relatively rapidly modifies the epidemiology of
diseases transmitted by these vectors and plays a key role
in the emergence and re-emergence of many diseases
around the planet.
The scientific community in Occitanie has internationally
recognised expertise in the field, as reflected by the
creation in Montpellier ofVectopole Sud, a centre of
excellence in France and Europe in crop pests and
vector arthropods that transmit pathogens able to cause
infectious human and animal diseases.The region’s scientists
equally collaborate closely with other research teams
around the world and have formed long-term relationships
that have led to the creation of centres of expertise in
key zones (e.g. inWest Africa, see box opposite). For
example, INTERTRYP studies the biology and ecology of
the tsetse fly, the vector for sleeping sickness, caused by a
parasite of the Trypanosoma genus, with a particular focus
on the vector’s adaptability to anthropized environments.
MIVEGEC is developing a deeper understanding of the
different species of mosquitoes that are vectors of malaria
(Anopheles mosquitoes) and the dengue, Chikungunya and
Zika viruses (Aedes mosquitoes). Several research projects
are being conducted in Gabon and Brazil on the possible
role of the Asian tiger mosquito Aedes albopictus as a
‘bridge vector’ between wild animals, domesticated animals
and humans.
For example, ASTRE has analysed the connection
between populations of Culicoides biting midges,
vectors of bluetongue viral disease (a disease that is
not transmissible to humans, but affects sheep and
other ruminants and has been responsible for massive
outbreaks since 1998 in the Mediterranean and
elsewhere in Europe), allowing them to retrace the
trajectory of the strains of the virus and uncover the
transmission pathways of the disease22
.
3. Understanding and
characterising disease vectors
The parasite
infects the liver
where it
multiplies
The parasites then
infects the host’s red
blood cells where it
multiplies, causing the
symptoms of the disease
The parasite
is transmitted to
another mosquito
taking a blood
meal
The parasite is
transmitted to a
human when the
mosquito takes
a blood meal
Mosquito
Culex genus
(vector)
Bird
(reservoir)
WEST NILEVIRUS
MALARIA PARASITE
Mammals
(accidental hosts)
The parasite mates
in the gut of the mosquito,
where it reproduces
and migrates to the
insect’s salivary glands
Examples of vector-borne pathogen cycles
By increasing understanding of
the biology and ecology of vector
species, scientists are contributing
to improving systems that prevent
and control diseases.
13. Disease vectors or crop pests:
it’s the same battle!
While certain insects carry infectious diseases, others feed on
plants (stems, leaves, fruits, etc.), resulting in significant crop
loss on an international scale. As global changes continue to
alter natural systems, the invasive behaviour of certain insect
pests risks being exacerbated.As with insects that are disease
vectors, the challenge lies in controlling their populations
– in this case to protect crops – while limiting the use of
insecticides, which are toxic not only to target insects, but to
beneficial insects such as pollinators and auxiliary insects that
feed on pests.
To tackle the issue from both fronts, research teams in
Montpellier working on arthropods of medical, veterinary
and agricultural interest joined forces to pool infrastructure
and expertise in Vectopole Sud, an international centre of
excellence with the aim of developing applications in early
warning systems, monitoring and control of arthropod disease
vectors and crop pests. In the area of plant health, DGIMI is
studying three species of noctuid moths:invasive Lepidopterans
whose polyphagous caterpillars damage a variety of food crops.
The mechanisms driving the interactions between the insects,
the pathogens and parasites associated with them, and the
host plants are being decoded.In the area of human and animal
health, mosquitoes, ticks, flies and midges that are vectors of
diseases with medical and veterinary impacts are the focus of
INTERTRYP, ASTRE and MIVEGEC, the latter being the
main laboratory of the national centre of expertise on vectors.
A double blow against crop pests
and vectors of human pathogens
Some agricultural environments are particularly favourable to
the proliferation of mosquitoes, particularly vegetable or rice
farms where water is present for extended periods. Female
mosquitoes seeking a place to lay their eggs are naturally drawn
to these areas of water, and are especially attracted if the water
contains fertilisers. MIVEGEC, a laboratory accredited as a
collaborating centre for the World Health Organisation on
pesticides and public health, is studying an innovative approach
that incorporates an insecticide in the fertiliser spread in fields
that would target both mosquito larvae and crop pests21
.
Agronomists, farmers and vector control services could thus
develop joint actions in this shared fight, which would be
technically and financially advantageous for all three parties and
would also reduce the impact of pesticides on the environment.
Detailed knowledge of vector biology and ecology
in a given socio-ecosystem is also essential to
implement the sterile insect technique, which
consists of releasing sterilised males raised in a
laboratory into the wild.These then mate with
females, which produce no offspring, reducing
the vector population.This technique has been
used to eliminate the tsetse fly, the vector of
Trypanosomes (which cause sleeping sickness in
humans, and animal trypanosomiasis, or ‘nagana’,
in livestock) in a targeted area of the Niayes
region in Senegal, through a collaborative project
between INTERTRYP, ASTRE, veterinary
services, the Senegalese Institute of Agricultural
Research, Senegal’s Ministry of Agriculture and
the International Atomic Energy Agency.The
methods and technologies developed, such as
the distribution models, the patented system for
aerial release, and quality control guidelines, will be
equally valuable in other African countries involved
in the Pan-African campaign to eliminate the tsetse
fly and trypanosomiasis that was launched in 2001
by the African Union23
.
A similar approach is being developed by MIVEGEC
to control the population of theAsian tiger
mosquito Aedes albopictus on the French island of
La Reunion24,25
.The stakes are high, as this mosquito
transmits dengue fever, and outbreaks continue
to spread into new geographical areas due to the
circulation of viral strains via infected travellers,
the introduction and persistence of these vector
mosquitoes in new territories, and their increasing
resistance to insecticides. More than 100 countries,
representing a quarter of the world population,
are today considered at risk of dengue epidemics.
Evolutionary biology research into the adaptation
of mosquitoes to different environments, an area
investigated by ISEM, opens other possibilities for
applied approaches in vector control: for example,
the use of the symbiotic bacteria Wolbachia (see
box).
Bacteria that live in symbiosis
with mosquitoes to control virus
transmission
Symbiotic bacteria of the Wolbachia genus develop in the cells
of arthropods and are transmitted generation after generation
by the female. In mosquitoes, embryos resulting from crossing a
male infected by Wolbachia and a female that is uninfected (or
infected by another incompatible strain of Wolbachia) are not
viable due to a phenomenon known as cytoplasmic incompatibility.
In addition, it has been demonstrated that mosquitoes with
Wolbachia are protected against certain viruses such as dengue,
thus reducing their ability to transmit these viral diseases to
people.By encouraging the reproduction solely of infected females,
cytoplasmic incompatibility considerably increases the spread of
Wolbachia, which can easily reach a prevalence of 100% in a natural
mosquito population.
A deeper understanding of the genetic factors of this incompatibility
– the research subject of ISEM and PIMIT – will optimise the
use of Wolbachia as an agent of vector control26,27
. This can be
based on one of two mechanisms: a ‘suppression’ strategy that
reduces the density of the vector by releasing male mosquitoes
infected by Wolbachia into a target population (as in the sterile
insect technique) or a ‘replacement’ strategy that replaces a
target mosquito population with individuals infected by a strain of
Wolbachia with a protective effect against infection by viruses that
are human pathogens in the aim of disrupting transmission.
The first approach (suppression) was tested in natural and
semi-natural conditions in Myanmar, in French Polynesia and in
Kentucky in the United States, resulting in a significant decrease
in the target mosquito population. The second approach
(replacement) is currently being trialled in Colombia, Brazil,
Indonesia and Vietnam in the framework of an international
programme with the aim of eliminating dengue fever, and is so far
showing promising efficacy.
11
14. The infection of a host by a pathogen requires physical
contact and a biological interaction between individuals.
These interactions require analysis on three interlinked
scales: at the cellular and molecular level, at the level
of individuals and populations, and at the level of the
landscape and the interconnection of species and the
environment (see diagram below).
Molecular interactions
The infection of a host by a pathogen occurs on a
cellular and molecular level. Many teams of scientists
are researching these processes.The goal is to describe
the entryways of a pathogen into a host organism,
the molecular interactions at work on both sides, the
virulence of the pathogen, and the immune response and
other defensive reactions activated in the host.
Research units including CPTP, IPBS, IRIM, VAP,
MIVEGEC, TRANSVIHMI and ASTRE are studying
interactions between animal hosts and pathogenic
bacteria (Brucella, Coxiella burnetii, Mycobacterium
tuberculosis, Leptospira, etc.), viruses (HIV, dengue,
Chikungunya, Zika, hepatitis E, influenza, measles, etc.),
and parasites (Toxoplasma, Plasmodium, Leishmania, Babesia,
etc.). Concerning tuberculosis, which is caused by
Mycobacterium tuberculosis bacteria, IPBS has discovered
several therapeutic targets for new antibiotics and is
participating in major European research programmes
into new vaccines that are more effective than the
current BCG vaccine. MIVEGEC is contributing to
investigating how human cells are infected by the Zika
virus, with the aim of identifying therapeutic targets
(see box opposite). Other research teams such as
LRSV, GAFL, BGPI, IPME and LIPM are studying the
interactions between plant hosts and pathogenic viruses,
bacteria, filamentous fungi and oomycetes (the latter two
are plant pathogens that cause different types of blight
and rot).
Typically, vaccination acts at different
interface levels: a vaccine reproduces on
a molecular scale the interaction between
the host and the pathogen, stimulating
the host’s natural defences (the immune
response). A vaccinated individual should
thus be resistant to the disease and be
individually protected. But the protection
of the wider population is only effective
when a critical proportion of individuals
are vaccinated, limiting the possibility of the
survival of the pathogen in its reservoirs
and thus the spread of the disease.
Differences in immunisation coverage of a
host population in a given region explain
why certain diseases have been eliminated
in certain regions but not in others.
The different scales of pathogen-host interactions
4. Understanding and
characterising interfaces
Understanding the molecular
interaction mechanisms between the
pathogen and the host is crucial in order
to identify therapeutic targets and to
develop treatments or vaccines.
12
Interaction at the level of individuals
and the population
Interaction at the level of the landscape
Interaction at the cellular
and molecular level
15. 13
Microorganisms for treatments
Microbial communities are also an important source of
therapeutic molecules: more than one out of two drugs
approved since 1940, and over 80% of anti-infection
and anti-cancer agents discovered since 1980 have
natural origins or were inspired by natural products, the
majority from microorganisms. Endophytic fungi, which
live symbiotically with plants, are good candidates for
these types of molecules.As they compete for their
living environment with other microorganisms, some of
which are harmful to the plant, it is in their interest to
prevent the proliferation of pathogens.This is why natural
selection has favoured their capacity to secrete antibiotic
molecules whose effect is to eliminate this competition.
While the fungi draw resources from the plant, in return
the plant is protected from pathogens, so each mutually
benefits.The PHARMA-DEV laboratory has isolated
new molecules from the achiote (Bixa orellana, a plant
cultivated in the Amazon for annatto, an orange-red food
colouring) that are very effective against leishmaniasis,
a vector-borne parasitic disease that affects both
humans and dogs in temperate regions and is present in
Occitanie28
.The development of a medicine for human
and veterinary use is being studied. In a similar approach,
LBBM in Banyuls-sur-Mer is researching the endophytic
fungi of Posidonia oceanica, a seagrass that is abundant in
the Mediterranean. PIMIT has also found that extracts
from certain plants on the island of La Reunion seem to
show promise against the Zika and dengue viruses (see
box above).
Since the first outbreak in Micronesia that revealed
the virus in 2007, Zika struck Polynesia at the end of
2013, affecting 55,000 people, and reached Brazil and
then the rest of South and Central America in 2015. An
international scientific consortium that includes MIVEGEC
recently revealed how the virus infects humans through
the vector of a mosquito (Aedes aegypti or albopictus) and
then propagates in the person affected29
.When a mosquito
‘bites’, it uses its proboscis (a needlelike mouthpart) to
search the skin for a blood vessel. When it finds one, it
pierces the skin to draw out blood, at the same time
depositing viral particles in the victim’s skin. The Zika
virus particularly infects a type of cell called a fibroblast,
where it replicates until the cell self-destructs and bursts.
This allows the virus to multiply in the organism and infect
other cells, and can eventually reach the foetus and the
nervous system. The cellular receptor that allows the
virus to enter a fibroblast has been identified, opening the
possibilities for developing a treatment.
Another interesting development has been made by
researchers from PIMIT: focusing on traditional medicine
in La Reunion, they found that extracts from ‘bois de
gouyave marron’ (Psiloxylon mauritianum) and‘bois de gaulette’
(Doratoxylon apetalum), two flowering plants native to the
island’s forests, have an inhibitory effect on infection by
several strains of the Zika virus, as well as on the dengue
virus30,31
. Experiments on in vitro cells show that these
plant extracts act on viral entry in the cells,one interfering
with the attachment of viral particles to host cells, and
the other with the internalisation of viral particles within
the cells, with no toxic cellular effects. These plants thus
seem good candidates for identifying antiviral compounds
that could be used in the fight against Flaviviruses of public
health concern.
How the Zika virus infects human cells
FIBROBLASTEPIDERMIS
DERMIS
1.The virus penetrates the dermis when
a mosquito takes a blood meal
2.The virus binds to a cellular receptor
of a skin fibroblast
3.The virus penetrates the cell
4.The virus replicates in the cell 5.The cell bursts, freeing the virus,
which then infects other cells
19. 17
In addition to the three spatial scales of interactions
between hosts and pathogens (molecular/cellular,
individual/intra-population, inter-population/landscape),
there is a temporal dimension: the modification over time
of environments and organisms.The Earth is a dynamic
system. Over long periods of time, continents move, the
climate changes, populations migrate, species evolve, and a
new equilibrium is created.
Microorganisms generally have a short generation time:
they reproduce in large numbers, which gives them high
evolutionary potential (through genetic recombination,
gene transfer or gene mutation) that depends on the
environmental and biological pressures they experience.
Over the long term, an interaction between a
microorganism and its host, whether mutually beneficial,
parasitic (beneficial to the parasite and harmful to the
host) or commensal (beneficial to the microorganism and
neutral for the host), can not only alter, but can change in
nature. Likewise, in the context of ‘cooperation’, a strategy
adopted by a large number of species in which individuals
generate resources used by the whole community,
‘cheaters’ can appear who profit from the resources
without participating in their production. In a parasitic
interaction, the virulence can be modified by increasing
the intensity of the pathogenicity. Hosts also evolve in
reaction to parasitic pressure, although often over a
longer time period (due to a more extended generation
time), and can naturally acquire new forms of resistance,
which pathogens then adapt to sidestep, and so on.
CEFE, ISEM and MIVEGEC are developing theoretical
and experimental approaches to better understand
the evolution of pathogens and their coevolution
with hosts.Transposing concepts based on long-term
coevolution processes to short time scales sheds new
light on the short-term responses of organisms to
changes in their environment and vice versa. For several
millennia, and particularly in recent decades, humankind
has considerably accelerated the pace of change on a
planetary scale: we have modified environments and land
use through agriculture, livestock rearing, urbanisation
and deforestation; we have disrupted the climate through
the atmospheric emission of greenhouse gases; we have
travelled to every part of the planet by every means,
bringing in our wake, intentionally or not, a whole array
of species; we have introduced chemical substances into
every environmental compartment (water, soil and air).
The period since the Industrial Revolution at the end of
the 18th century, in which human activities have made
a significant global impact on the Earth’s ecosystems,
is considered a new geological epoch, called the
Anthropocene.
5. Understanding and
characterising emergence
mechanisms
These disturbances, generally
referred to as ‘global changes’, equally
have an impact on the emergence and
transmission of diseases, as shown in
the diagram above.
Factors that can lead to the emergence of epidemics
Introduction of a
pathogen or vector in an
environment where it was
not previously present
Introduction of the
Asian tiger mosquito from
Southeast Asia to Africa in
2000 and to France in 2004
Relatively warm and wet
winter
Favourable environmental
conditions
Mutation Mutation
Low-virulence
bacteria
Virus
infects
host 1
but not
host 2
Virus
infects
host 1
and
host 2
Population
resistant
Population
susceptible
High-virulence
bacteria
Unfavourable environmental
conditions
Plant is resistant:
limited symptoms
Plant is susceptible:
severe symptoms
Maintenance of mosquito
population over the winter
Proliferation of mosquito
population in the
warm season
Proliferation
of a pathogen or
vector due to changing
environmental conditions
Environmental conditions
weaken host defenses
Mutation of the pathogen,
leading to increased
virulence or resistance
to treatment
Mutation of the pathogen,
leading to host jumping
20. 18
Introduction of vectors and pathogens
Global changes can lead to the introduction of a new
pathogenic agent or a new vector in an environment
where it was not previously present. For example,
MIVEGEC is studying the introduction and proliferation
of the Asian tiger mosquito Aedes albopictus, the vector of
emerging arboviruses such as dengue and Chikungunya.
Native to Southeast Asia, this mosquito species first
appeared in continental Africa in the 2000s, on mainland
France in 2004, and in southwest France in 2008 – in
each of these areas, it has become highly invasive.Aside
from the inconvenience caused by this mosquito due
to its abundance and aggressiveness, now the risk of
viral transmission linked to travellers returning from
endemic areas must be considered. In 2014, the city
of Montpellier faced an autochthonous episode of
infection by the Chikungunya virus48
, and in 2015, several
autochthonous cases of dengue fever were detected in
the Gard, a department in Occitanie49
.Another example
is the introduction and proliferation in Thailand of the
New Guinea flatworm, a free-living trematode, which has
become a vector for a pre-existing nematode that is a
parasite of humans and rats and causes meningitis (the
local reservoir in Thailand is a snail).This introduction
is being studied by scientists at Thailand’s Mahidol
University and ASTRE, who are drawing on a network of
Thai citizens to map the presence of the new vector and
monitor its evolution in the goal of prevention50
.
Proliferation of existing vectors and pathogens
Global changes, by modifying the environment, can also
favour the proliferation of pre-existing pathogenic agents
or vectors, as observed by MIVEGEC on the island of La
Reunion in 2018 during an outbreak of dengue fever.The
dengue virus is present on islands in the southwestern
Indian Ocean, which experience recurrent epidemic
episodes during the rainy season, with the number of
cases generally decreasing during the austral winter, in
line with the reduced density of vector mosquitoes. But
at the end of 2017 in La Reunion, observers noted the
persistence of dengue transmission hotspots in the west
of the island after the winter, leading to a major outbreak
in the hot, rainy season at the beginning of 201851
.The
Asian tiger mosquito (Aedes albopictus), the dominant
species on the island, was the suspected vector in the
transmission of this epidemic, although the principal
vector species (Aedes aegypti) is also present in residual
populations restricted to certain zones.These extremely
localised populations require monitoring, as expansion is
always a risk.
Weakening of host defences
Global changes can also result in weakening a host’s
capacities of defence, as LIPM and IPME have shown
in plants (see box below). In their natural environment,
plants are exposed to both biotic stress (insects, fungi,
bacteria, viruses, etc.) and abiotic stress (variations
in temperature, the quantity and quality of light, the
availability of water and minerals, pollution, etc.), which
can occur sequentially or simultaneously. Plant reactions
to these types of stress have been widely studied and
well described in simple systems, often involving a
single plant species and a sole type of stress. However,
the response of plants to a combination of stressors
remains poorly understood. Climate change scenarios
predict an increase in the average temperature of 1.5
to 4.8°C between now and the end of the century
along with a rise in the frequency of extreme climate
events, which will, in certain contexts, accentuate
abiotic stress on plants. Global changes also increase
the risk of the emergence of pathogens, amplifying
biotic stress. Moreover, various resistance mechanisms
employed by plants are inhibited by a constant increase
in temperature.
LIPM is researching the impact of rising temperatures on the interactions between the soil bacterium Ralstonia
solanacearum, which causes bacterial wilt in more than 200 plant species, and the tomato (Solanum lycopersicum L.) and
thale cress (Arabidopsis thaliana).These plants are used as models to address the following questions52
:What mechanisms
inhibit the immune responses of plants in conditions of increased temperatures? What are the genetic factors in the
resistance mechanisms to withstand increased temperatures? What role does the root microbiota play in plant–
pathogen–environment interactions?
Another experimental study conducted by IPME aims to identify the influence of environmental conditions on the
capacity of coffee plants to resist a pathogenic fungi (Hemileia vastatrix) that causes coffee leaf rust.The results indicate
that, cultivated in an optimal environment, plants that are genetically vulnerable to this fungi were nonetheless able to
resist it53
. So well in fact that when their needs were met (in terms of water, minerals, temperature conditions, etc.),
plants in the field displayed a level of resistance to pathogens sufficient to avoid pesticide use.In contrast,there is concern
that stressful environmental conditions (drought, heatwaves, excessive water leading to increased parasitic pressure,
etc.) weaken the plant’s natural defences and exacerbate harm to its health. Researchers have identified an indicator of
the general health of the plant, capable of predicting its ability to resist infection by a pathogen, based on ‘chlorophyll
fluorescence’, which is easily measurable with a small portable tool54
.The next step is to use this predictive technology
directly in the field in order to verify its potential.
Plant-environment interactions
and pathogen resistance
24. Analysing, preventing and controlling
epidemics: integrated approaches
to health in action
While integrated approaches to health are essential
to enhance health security on national, regional and
global scales, their adoption currently remains limited
on an operational level. It is crucial to develop relevant
tools, methods, standards and recommendations
to help countries – particularly those that are less
advanced – and institutions to turn a systemic vision of
health into reality.These relatively new approaches are
not straightforward and require higher awareness by
stakeholders, active collaboration, and genuine integration
between the disciplines and sectors concerned through
strengthened policies and practices at each interface.
Effective pooling of existing infrastructure, information,
capacity and skills in different sectors (e.g. policymakers
and managers in public, veterinary and environmental
health) and compartments (e.g. human, animal/
plant, environment) is vital. For example, the role
of social science in controlling the Ebola epidemic
since its outbreak in West Africa (2014–2016) has
been recognised by the World Health Organisation.
Anthropologists are now included in the rapid response
teams deployed in public health emergencies, and
international organisations advocate for the inclusion of
social sciences in a ‘One Health’ perspective.Yet there
are many challenges: these involve bringing on board
researchers from a minority disciplinary field, fostering
interdisciplinary dialogue with biomedicine, reinforcing
research units in developing countries with insufficient
doctoral training, and creating links with specialists
in environmental anthropology and health, all while
ensuring scientific excellence63
.
Integrated health approaches rely on enhanced cooperation
between stakeholders and sectors
1. Creating a favourable
collaborative environment
22
Source: adapted from a Centre for Disease Control and Prevention
People who protect
human, animal and
environmental health and
other partners
To achieve the best health
outcomes for people,
animals, plants and the
environment
Integr
ated health appro
aches
Coordinating
Collaborating
Communicating
25. 23
Stakeholder networks
In practice, this means bringing together different
stakeholders and sectors within networks, observatories,
platforms, training centres, etc. that allow the
dissemination of the principles of the integrated
approaches to health and facilitate their implementation
and their governance.A number of networks have been
created to this effect at different levels, for example:
On an international level, a tripartite collaboration
between the United Nations Food and Agriculture
Organisation (FAO), the World Organisation for Animal
Health (OIE) and the World Health Organisation
(WHO) recently reaffirmed its commitment to
multisectoral cooperation on the risk of disease at the
human–animal–environment interface.
During the Ebola outbreak in West Africa,
anthropologists from a dozen countries created a
network that became in 2016 the Anthropology of
Emerging Epidemics Network, a space for exchange
and mutual support. Based on the comparative
approach at the heart of anthropology, the network
developed the programme ‘Comparative anthropology
of the Ebola epidemic’, in which TRANSVIHMI
participates.The results of the social science analyses
carried out by members of the network were used to
adjust and humanise the strategies and procedures of
both risk and crisis management put in place post-
Ebola by health institutions (Ministries of Health and
Health Emergency Operation Centres) in five African
countries (Senegal, Burkina Faso, Ivory Coast, Benin,
Guinea) and in France (High Council of Public Health).
In 2019, this network expanded worldwide to facilitate
access, information sharing and the deployment of
social sciences in dealing with outbreak risks. Other
actions to enhance the integration of social sciences in
health strategies are being developed for the benefit of
scientists and institutional stakeholders.
To tackle antimicrobial resistance on a global level, it is
fundamental to take into account the problems unique
to developing countries and to consider specific local/
regional characteristics.To this end, the French National
Alliance for Life Sciences and Health (Aviesan) has
started building a research network with developing
countries in the framework of the French government’s
Priority Research Plan on antimicrobial resistance.
In order to facilitate the development of joint projects,
countries with a tradition of working with French
medical and veterinary research institutes (e.g. IRD
with TRANSVIHMI and MIVEGEC, Cirad with
ASTRE, Inserm and the Institut Pasteur International
Network) have been targeted in priority: Cambodia,
Ivory Coast, Madagascar.The more long-term objective
is to build on this core group by involving other
developing countries, creating a co-financed programme
of operational, multidisciplinary research combining
epidemiology, medicine, biology, humanities and social
sciences.Three research topics have been prioritised:
- access to community care, irrational distribution and
use of antibiotics, and the circulation of counterfeit
drugs;
- hospital care for community-acquired infections and
the significant impact of inadequate first-line
treatment and empiric therapy protocols;
- practices around the use of antibiotics in animal
health and on farms and the conditions for the
transmission of resistance.
In the Mediterranean basin, the European project
‘MediLabSecure’, coordinated by the Institut Pasteur
in Paris and in which MIVEGEC participates, aims
to reinforce the preparedness in responding to viral
outbreaks – medical or veterinary – of a network of
laboratories in 19 European and non-European
countries around the Mediterranean and the Black
Sea.The research topics focus on the evaluation of
risks, the optimisation of integrated surveillance and
control strategies, in particular of vector-borne
diseases, as well as skills development and increasing
regional awareness of these diseases through training
and information sharing between partners.
On the French island of Guadeloupe in the Caribbean,
10 institutes have joined forces in the collaborative
project MALIN (including ASTRE and BGPI)
to better control infectious human, animal and plant
diseases through a multidisciplinary approach
combining microbiology, entomology, epidemiology
and socio-economics.This project aims to improve
knowledge, diagnosis and surveillance of infectious
human, animal and plant diseases that affect the
territory; to develop alternative and sustainable control
methods for these diseases; to assess their economic
and social impact; and finally to transfer the innovations
arising from the project to concrete actions and
training.
Epidemic preparedness
Health actors, researchers, governmental agencies,
NGOs and the United Nations all agree that epidemic
preparedness is essential to prevent outbreaks and
reduce their damage. Since 2016, health emergency
preparedness systems have been put in place in all
African countries.These include the establishment of
epidemiological surveillance systems – particularly in
communities – and early warning systems, the training
of health professionals (human and veterinary) for crisis
response, the development of diagnostic capacities, the
organisation of crisis management structures, and the
reinforcement of hospital units that respect biosecurity
rules (e.g. triage, isolation) and can provide treatment
(prepositioned stocks of medicines and equipment).